Wrinkle reduction

ABSTRACT

Wrinkles are cosmetically removed from a superficial area of mammalian skin tissue having an epidermal layer, a basal layer, and a dermal layer, by irradiating the dermal layer through the basal layer, the irradiation being selected to be absorbed by a chromophore in the dermal layer such that collagen present in the dermal layer is heated, while the basal layer remains intact so as to substantially inhibit contact of the dermal layer with ambient air.

[0001] This is a Continuation In Part of U.S. patent application Ser.No. 08/919,472 Filed on Aug. 28, 1997.

BACKGROUND TO THE INVENTION

[0002] The present invention relates to a method of reducing wrinklesfrom a superficial area of mammalian skin tissue, and apparatustherefor.

[0003] The application of laser technology in healthcare is well known,and the use of lasers in medical applications has been studiedextensively since the early 1960's. In recent years an increasinginterest has been shown in cosmetic applications. Two such cosmeticapplications are skin resurfacing and wrinkle removal; in this fieldlasers can be used as an alternative to surgical facelifts.

[0004] There is a distinct difference between wrinkle removal and skinresurfacing. Skin resurfacing is where laser energy vaporizes thinlayers of the epidermis without breaking through the basal layer intothe dermis. This is essentially a superficial process primarily used togive the skin a “fresher” appearance. However, wrinkle removal as a moreaggressive technique where tissue is removed layer by layer, invadingthe dermis and effectively inducing a second degree burn. Heat isdeposited in the dermis shrinking the collagen and tightening the skin.

[0005] In young skin, the collagen just beneath the surface of the skinforms an organized lattice with good elasticity and flexibility. Duringaging, the collagen changes its structure impacting negatively on thecosmetic appearance of the skin. Several techniques have been developedto induce a “controlled injury” to the dermis in an attempt to generaterejuvenation of the collagen structure returning the skin to an earliercosmetic appearance. During the 1990's a laser approach to wrinkleremoval has been introduced.

[0006] For known wrinkle removal techniques, the wavelength is chosen sothat the laser energy is highly absorbed in water, the current lasers ofchoice being the CO₂ laser at 10.6 μm wavelength and the Erbium YAGlaser at 2.94 μm wavelength. In this non-selective process, pulses oflaser energy are applied to the skin surface, each pulse vaporizing alayer of tissue between 30 μm to 60 μm in thickness. Normally, the firstpass of the laser removes a thin layer of the epidermis without damagingthe basal layer. Successive passes over the same area penetrate into thedermis and heat the collagen. The laser operator sees this thermalbuild-up “shrink” the skin in “real time”, tightening up the skin'sappearance. When the desired clinical outcome is achieved, the operatorceases applying laser pulses. It is therefore apparent that the qualityof the cosmetic result is highly dependent upon the experience and skillof the operator.

[0007] In the case of CO₂ laser wrinkle removal, post-treatmentsupervision of the patient is a necessity. Immediately after treatment,the skin is essentially an open wound requiring dressings in place for2-10 days. Additionally, topically applied lotions are required forpatient comfort and prevention of infection. Post-operative infection iscommon, primarily due to removal of the natural protective barrier ofthe skin, with a reported incidence of between 4.5 to 7%.

[0008] On average, with CO₂ laser wrinkle removal, post-treatmenterythema is present for 4-5 months. This compares to 2-3 monthsfollowing a Chemical Peel. Also, the incidence of side effects issignificant, the most common being hyperpigmentation occurring in 30-40%of cases. Higher incidences are reported in darker skin types. A delayedhypopigmentation, which can occur up to a year after the procedure wasperformed, has recently emerged as a complication of aggressive laserresurfacing. Many of the eminent laser resurfacing surgeons haveresorted to less aggressive techniques.

[0009] The effect of known procedures is two fold:

[0010] (a) the laser induces denaturing of the collagen in the dermis,and the formation of cross links, which results in a tightening effectstretching the skin, reducing or removing the wrinkles (it is thoughtthat the thermal threshold for this effect is a temperature of 70° C.);and

[0011] (b) the changes to the dermis induce the generation of newcollagen which develops using the matrix created by the denaturedcollagen as a foundation.

[0012] The skin-resurfacing and wrinkle removal procedure outlined aboveis considered by many experts in the field as a significant improvementover previously used surgical methods. The procedure uses the laser'sability to deliver high energy density at the surface of tissue andhence ablate the surface tissue in a well controlled manner. Continuingto remove the tissue, layer by layer is designed to damage the collagenand hence induce wrinkle removal. This second stage of the procedure isprimitive; the skin weeps, scabs form and redness of the skin appearsfor many weeks.

OBJECT OF THE INVENTION

[0013] It is therefore the primary object of the present invention toprovide a technique for removing wrinkles from a superficial area ofmammalian skin tissue without causing secondary burns and other problemsassociated with traditional wrinkle removal.

SUMMARY OF THE INVENTION

[0014] The present invention provides a method of removing wrinkles froma superficial area of mammalian skin tissue. The dermal layer of thetissue is irradiated through the basal layer by radiation selected to beabsorbed by a chromophore in the dermal layer such that collagen presentin the dermal layer is heated, while the basal layer remains intact soas to substantially inhibit contact of the dermal layer with ambientair.

[0015] According to a further aspect, the invention provides apparatusfor cosmetic reduction of wrinkles on a superficial area of mammalianskin, the apparatus comprising a radiation delivery system fordelivering a radiation beam of predetermined monochromatic wavelength ornarrow wavelength bandwidth to the skin, the radiation delivery systemincluding a pulsation system for pulsing the radiation deliveredaccording to a predetermined regime, and an optical arrangement forfocussing the beam such that the total radiation energy densitydelivered to the skin is substantially in the range 0.5 J/cm² to 5 J/cm²per pulse.

[0016] The irradiation of the dermal layer in the method according tothe invention is tailored to shrink the skin tissue without damage tothe dermis (in other words, without causing second degree burns) becausethe barrier provided by the basal layer remains intact. This is achievedby selecting the required radiation wavelength to match thecharacteristic absorbtion wavelength of the chromophore whilst beingabsorbed to an insignificant degree in the epidermis and basal layer.The energy delivered per pulse is also tailored to ensure that ablationdoes not occur of the target structure, but rather that energy absorbedin the target provides sufficient heating that heat energy diffusingoutwards from the target heats the surrounding tissues to a degreesufficient to thermally induce shrinkage of the surrounding tissue andalso stimulate the production of new tissue components such as elastinand collagen.

[0017] If the target for the laser has an appropriate chromophore (asubstance that absorbs a specific wavelength and transmits or scattersat other wavelengths) then the laser can be used to modify that targetselectively within an inhomogeneous volume of tissue. Occasionally, thedesired target does not have a suitable chromophore of its own butexists in close proximity to another material which has such achromophore which can be selectively targeted. Such interaction iscalled secondary selective interaction.

[0018] An artificial chromophore may be introduced into the desired areafor wrinkle reduction, or a naturally occurring chromophore may beselected. In a preferred embodiment of the technique, the naturallyoccurring chromophore selected is oxyhemoglobin of the dermal plexuswhich has wavelength absorbtion peaks at 585 nm and 815 nm, at whichwavelengths absorbtion in surrounding tissue components is relativelylow.

[0019] According to a further aspect, the invention therefore providesapparatus for cosmetic reduction of wrinkles on a superficial area ofmammalian skin, the apparatus comprising a radiation delivery system fordelivering substantially monochromatic radiation in a bandwidth ofsubstantially 15 nm or less in at least one of the ranges 570 nm to 600nm and 750 nm to 850 nm, the delivery system including a pulsationsystem for pulsing the radiation delivered according to a predeterminedregime in which the energy density of the substantially monochromaticradiation in the bandwidth of substantially 15 nm or less delivered tothe skin is substantially in the range 0.5 J/cm² to 5 J/cm² per pulse.

[0020] The method according to the invention is non-invasive andnon-ablative and can readily be performed by non-medical personnel. Thetotal energy delivered per pulse is sufficient to effect the requiredphysical change in the tissue surrounding the target chromophore withoutcausing ablation of the target or other skin components through whichthe radiation passes.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0021] The radiation is preferably substantially monochromatic or atleast of a relatively narrow wavelength bandwidth to ensure that it ispreferentially selectively absorbed by the target chromophore. A lasersource may be used to produce the required wavelength, or a lightsource, such as an LED may be used with appropriate filtering to permitthe selected wavelength (or narrow wavelength band) to pass.

[0022] The irradiation may be by means of a source of visible orinfra-red radiation (suitably filtered to remove deleteriousultra-violet radiation if necessary). The radiation may be coherent(that is from a laser source). Such a laser source may be, for example,a dye laser, a ruby laser, or a semiconductor laser. If a dye laser isused, its wavelength is preferably such that it is absorbed byoxyhemoglobin (as naturally occurring chromophore present in bloodvessels in the dermis). Alternatively, the superficial area may betreated with an artificial chromophore which is absorbed into the dermallayer. Such an artificial chromophore may be applied to the epidermallayer in the form of a liposome-containing topical formulation. Thechromophore may then permeate through the basal layer for delivery tothe dermal layer.

[0023] When a laser is used, it may be arranged to scan the superficialarea and/or to irradiate the dermal layer in pulses. When the laser isin pulsed mode, the pulses typically have duration of 10 μsec to 10 msec(more preferably 200 μsec to 1 msec).

[0024] It is sometimes desirable to remove part of the epidermis priorto irradiating the dermal layer according to the invention. Suchepidermis removal (known as skin resurfacing) may be effectedmechanically (for example by abrasion), or by means of laser radiation.When laser radiation is used for this purpose, it is typically a scannercontrolled CO₂ laser source.

[0025] The energy density per pulse is preferably accurately controlledto ensure that a maximum threshold level (substantially of 5 J/cm²) isnot exceeded.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026]FIG. 1 is a schematic representation of the three outermost layersof mammalian skin tissue;

[0027]FIG. 2 is a schematic representation of partial removal of theepidermis (skin resurfacing), which is an optional step according to theinvention;

[0028]FIG. 3 is a schematic illustration of the result of a prior artmethod of wrinkle removal, which is surgical because it involves fullremoval of the epidermis in a selected area and therefore exposure ofthe dermis and consequent second degree burning;

[0029]FIG. 4 is a schematic illustration of the result of the methodaccording to the invention, showing that the epidermis is partiallyintact and the basal layer fully intact;

[0030]FIG. 5, is a schematic diagram of a first embodiment of wrinklereduction apparatus according to the invention;

[0031]FIG. 6 is a schematic diagram of an alternate embodiment ofwrinkle reduction apparatus according to the invention;

[0032]FIG. 7 is a schematic representation of an optical delivery systemforming part of apparatus according to the invention; and,

[0033]FIG. 8 is a graphical representation showing the intensity profileof the radiation delivered using apparatus according to the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0034] Referring to FIG. 1, the basic skin structure of mammalian skintissue comprises three layers, the outermost epidermis 1 which isadjacent to the basal layer 2 and then the dermis 3.

[0035] Referring to FIG. 2, partial removal of an area 4 of epidermis 1by means of CO₂ laser radiation is known as skin resurfacing. This stagerepresents the first step of a prior art method but is an optional stepaccording to the invention. Both the basal layer 2 and the dermis 3 areunaffected by the laser radiation.

[0036] As shown in FIG. 3, prior art method of wrinkle removal resultsin complete removal of an area 5 of epidermis 1 and basal layer 2 byrepeated exposure to CO₂ laser radiation. Partial removal of the dermis3 also occurs, as represented by 6, leaving the dermis exposed to air.This causes a second degree burn which is slow to heal and a risk ofinfection.

[0037] As shown in FIG. 4, the method of wrinkle removal according tothe invention results in partial removal of the epidermis 1 (this is anoptional step as described in FIG. 2 above) and the basal layer 2 isleft intact, such that the dermis 3 is not exposed to air. Laserradiation 7 is applied to the tissue and selectively absorbed by achromophore in the dermis 3, heating the collagen and shrinking the skinhence removing the appearance of wrinkles.

[0038] In a preferred embodiment, the target chromophore selected isoxyhemoglobin in the dermis 3 which has absorbtion peaks atapproximately 585 nm and 815 nm. The apparatus shown in FIG. 5 comprisesa laser radiation delivery system 101 comprising a flashlamp excitedpumped dye laser including a laser head 102, dye reservoir 103 and pump104. A flowmeter 105 regulates dye flow to the laser cavity in the laserhead 102 and a cooling system 106 cools the laser head 102 and dyereservoir 103. The system is controlled by a microprocessor controller107 which operates voltage control of a pulse forming network 108(including a capacitor and inductor network) which initiates a dischargepulse and consequently a pulsed beam laser output from laser head 102.Voltage control and feedback is provided between the microprocessorcontroller 107 and pulse forming network 108 via link 109. Temperaturemonitoring feedback is provided between the cooling system and thecontroller 107 via link 110.

[0039] The laser head operates to output controlled pulses of laserradiation having wavelength in the range 577 nm to 585 nm and a pulseduration in the range 200 μs to 1 ms. To produce the required wavelengthan appropriate laser dye is selected (such as Rhodamine 575 orPyromethene 590), the concentration of the dye solution is controlled.

[0040] Control of the pulse duration for the dye laser arrangement 101is achieved by accurate control of the energy delivered to the excitingflashlamps in the laser head 102 by tailoring the capacitor and inductorvalues in the pulse forming network 108.

[0041] The energy is delivered to the skin surface via a fiberoptic tube112 (see FIG. 7) and a focussing optical lens arrangement 113 which isconfigured to focus a light spot onto the skin tissue surface so as tohave a spot diameter within the range 1 mm to 10 mm, and an intensitydistribution across the spot diameter that is substantially uniform(i.e. “a top hat” distribution), as shown in FIG. 8. Providing optics toensure that the uniform energy distribution results in even heating ofthe tissue without the occurrence of “hot spots” which could result intissue damage/oblation.

[0042] The radiation parameters are also selected to ensure that thetotal radiation energy density delivered per pulse falls within therange 0.5 J/cm² to 5 J/cm². It is particularly important that theselected upper threshold value (5 J/cm²) is not exceeded significantlyas delivery of a higher energy densities of radiation per pulse canresult in unwanted effects on the skin (such as ablation and/or otherdamage).

[0043] For the dye laser system 101 of FIG. 1, the energy density of theradiation delivered to the skin is controlled by adjustment of theflashlamp output energy (which in turn controls the laser outputenergy). The laser output energy in conjunction with the spot sitedetermines the energy density delivered. Accurate control is achieved bycontrol of the dye circulation rate, the dye temperature and theflashlamp output energy. Dye circulation rate is important becauserepeated pulsing of the same volume of dye, without circulation, reducesthe output energy of the laser head 102. Increasing or decreasing thedye temperature has an affect on the energy output of the laser head102. The flashlamp output energy is controlled by varying the voltagewith which the capacitors in the pulse forming network 108 are charged;feedback of the capacitor voltage via link 109 is therefore important.

[0044] The energy density required will vary within the specified rangefrom person to person, depending upon skin colour.

[0045] Referring to FIG. 6, there is shown an alternative embodiment ofapparatus for performance of the invention in which an LED orsemiconductor laser device 202 may be utilised to produce the outputradiation 220. A user interface 213 enables input into a microprocessorcontroller 207 which is used to control a power supply unit 214 toensure that the required current is supplied to the LED or semiconductorlaser device 220. A temperature sensor 215 provides temperature feedbackvia a link 210. Output 216 from controller 207 sets the current suppliedby the power supply unit 214 to the device 202; input 217 into thecontroller 207 provides current monitoring feedback. Control of thepulse duration is achieved by pulsing the current supply from powersupply unit 214 to the LED or semiconductor laser device 202.

[0046] High intensity LED devices are capable of producing wavelengthscorresponding to the 585 nm absorption peak of oxyhaemoglobin. Theoptical system (including lens 113) may include filters arranged tonarrow the band of radiation passing from the LED to the target area ofthe skin. Where lasers are used, the output may be monochromatic.Alternatively, or in the case where LED's are used, the radiationdelivered may be “effectively” monochromatic, or of a relatively narrowband width (typically within a band width of 15 nm or less).

[0047] Where a semiconductor laser device is used, the output maycorrespond to the second (higher) absorption peak (815 nm) foroxyhaemoglobin.

[0048] Whilst the invention has been described in relation to deliveryof effectively monochromatic radiation (or within specific narrow bandwidths) at one or other of the oxyhaemoglobin absorption peaks of 585 nmand 815 nm, it is clear that the beneficial effect of the invention canbe achieved to a certain degree by using wavelengths relatively closeto, but either side, of the respective absorption peaks. Preferredwavelength ranges for operation are 570 nm to 600 nm and 750 nm to 850nm for targeting oxyhaemoglobin.

[0049] Where an artificial chromophore is used, the wavelength (ornarrow band of wavelengths) is selected to correspond to acharacteristic absorption wavelength of the relevant chromophore. Itremains important to ensure that the total energy delivered per pulse isbelow the threshold damage level (approximately 5 J/cm²).

[0050] In the embodiments described, it is important to ensure thatthere is not excess energy (and therefore heat) build-up in the target,and therefore the inter pulse duration is selected at a level to avoidthis situation occurring. It is preferred that the pulse repetition rateis substantially in the range 3 Hz maximum or less.

1. Apparatus for cosmetic reduction of wrinkles on superficial mammalianskin, the apparatus comprising a radiation delivery system fordelivering substantially monochromatic radiation, said radiation beingin a wavelength bandwidth of substantially 15 nm or less and in at leastone of the ranges 570 nm to 600 nm and 750 nm to 850 nm, the deliverysystem including a pulsation system for pulsing the radiation deliveredaccording to a predetermined regime in which the radiation delivered tothe skin has an energy density substantially in the range 0.5 J/cm² to 5J/cm² per pulse.
 2. Apparatus according to claim 1, wherein theradiation delivery system is set up to deliver the substantiallymonochromatic radiation in a bandwidth of substantially 15 nm or lesssubstantially in at least one of the ranges 577 nm to 585 nm and 800 nmto 815 nm.
 3. Apparatus according to claim 1, wherein the radiationdelivery system is set up to deliver radiation in a concentrated beamhaving a cross-section with a substantially uniform energy distributionacross said beam cross section.
 4. Apparatus according to claim 1,wherein the radiation delivery system is set up to deliver radiation ina concentrated beam having a diameter substantially in the range 1 mm to10 mm.
 5. Apparatus according to claim 1, wherein the pulsation systemis set up to provide radiation pulses each pulse having a durationsubstantially in the range 10 μs to 2 ms.
 6. Apparatus according toclaim 1, wherein the pulsation system is set up to provide radiationpulses each pulse having a duration substantially in the range 200 μs to1 ms.
 7. Apparatus according to claim 1, wherein the radiation deliverysystem comprises a laser radiation delivery system.
 8. Apparatusaccording to claim 7, wherein the laser radiation delivery systemcomprises a dye laser radiation delivery system.
 9. Apparatus accordingto claim 8, wherein the dye laser radiation delivery system comprises aflashlamp pumped dye laser including a pulse forming network arranged topulse the laser according to the predetermined pulse regime. 10.Apparatus according to claim 7, wherein the laser radiation deliverysystem comprises a semiconductor laser radiation delivery system. 11.Apparatus according to claim 1, wherein the radiation delivery meansincludes a radiation emitting LED device.
 12. Apparatus according toclaim 11, wherein the radiation delivery means includes at least oneradiation filter arranged to filter radiation to permit thesubstantially monochromatic radiation to be delivered to the skin. 13.Apparatus according to claim 1, further comprising a control systemarranged to permit the energy density to be varied within the range 0.5J/cm² and 5 J/cm².
 14. Apparatus according to claim 13, wherein thecontrol means is arranged to inhibit selection of an energy densitysubstantially above 5 J/cm².
 15. Apparatus for cosmetic reduction ofwrinkles on a superficial area of mammalian skin, the apparatuscomprising a radiation delivery system for delivering a radiation beamof predetermined monochromatic wavelength or narrow wavelength bandwidthto the skin, the radiation delivery system including a pulsation systemfor pulsing the radiation delivered according to a predetermined regimesuch that the total radiation energy density delivered to the skin issubstantially in the range 0.5 J/cm² to 5 J/cm² per pulse.
 16. Apparatusaccording to claim 15, which includes an optical arrangement forfocussing the beam.
 17. A method of cosmetically removing wrinkles froma superficial area of mammalian skin tissue having, in the orderspecified, an epidermal layer, a basal layer, and a dermal layer, whichmethod comprises: irradiating said dermal layer through said basal layerby means of visible or infra-red radiation, said irradiation beingselected to be absorbed by a chromophore in said dermal layer such thatcollagen present in said dermal layer is heated, while said basal layerremains intact so as to substantially inhibit contact of said dermallayer with ambient air.
 18. A method according to claim 17, wherein theirradiation is from a substantially monochromatic radiation source in abandwidth of substantially 15 nm or less.
 19. A method according toclaim 17, wherein said irradiation is from a coherent radiation source.20. A method according to claim 17, wherein the source comprises a rubylaser arranged to target the dermis.
 21. A method according to claim 17,wherein the source comprises a dye laser of wavelength selected totarget oxyhemoglobin present in blood vessels in said dermal layer. 22.A method according to claim 17, wherein the source comprises a dyelaser, a ruby laser, or a semiconductor laser which scans said area ofmammalian skin tissue.
 23. A method according to claim 22, wherein thelaser comprising said source is pulsed.
 24. A method according to claim23, wherein the pulsed laser has pulses of duration 10 μsec to 2 msec.25. A method according to claim 17, in which said superficial area ofmammalian skin tissue is treated with an artificial chromophore which isabsorbed into the dermal layer.
 26. A method according to claim 25,wherein the artificial chromophore is applied to the epidermal layer inthe form of a liposome-containing topical formulation.